Yang Ning, Xiong Lijuan, Guo Ya, Chen Xiting, Wan Ning, Xie Bo, Zhou Juan
Department of Oncology, General Hospital of Southern Theater Command, Guangzhou, China.
Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, China.
J Thorac Dis. 2025 Jul 31;17(7):4826-4836. doi: 10.21037/jtd-2025-644. Epub 2025 Jul 25.
The efficacy of immunotherapy in programmed death-ligand 1 (PD-L1)-negative advanced lung adenocarcinoma remains controversial, with responsive subgroups poorly characterized. This study aimed to identify predictive subgroups through thyroid transcription factor-1 (TTF-1) expression stratification.
We retrospectively analyzed 253 consecutive PD-L1-negative advanced lung adenocarcinoma patients treated between January 2018 and January 2024. Outcomes of TTF-1-positive and TTF-1-negative patients receiving chemoimmunotherapy chemotherapy alone were compared. Cox multivariate analysis evaluated the prognostic impact of treatment regimens.
In the overall cohort, chemoimmunotherapy improved median progression-free survival [PFS: 7.9 6.6 months, hazard ratio (HR) =0.74, P=0.03] and overall survival (OS: 17.5 15.4 months, HR =0.69, P=0.02) compared to chemotherapy. Stratified by TTF-1 status, TTF-1-negative patients (n=66) receiving chemoimmunotherapy exhibited significantly superior PFS (7.5 4.8 months, HR =0.44, P=0.002) and OS (16.2 11.5 months, HR =0.44, P=0.005), whereas TTF-1-positive patients (n=187) showed no significant survival differences (PFS: 8.0 7.3 months, HR =0.88, P=0.42; OS: 18.7 18.3 months, HR= 0.86, P=0.44). Multivariate analysis confirmed chemoimmunotherapy as an independent favorable prognostic factor for TTF-1-negative patients [PFS: adjusted HR (aHR) =0.44, 95% confidence interval (CI): 0.24-0.81, P=0.008; OS: aHR =0.48, 95% CI: 0.25-0.90, P=0.02], but demonstrated no significant association in the TTF-1-positive cohort (PFS: aHR =0.93, 95% CI: 0.68-1.28, P=0.66; OS: aHR =0.91, 95% CI: 0.62-1.35, P=0.64).
TTF-1 expression may be a useful predictive biomarker for chemoimmunotherapy benefit in PD-L1-negative lung adenocarcinoma, pending further validation. TTF-1-negative patients demonstrated improved survival with chemoimmunotherapy (especially taxane-based regimens) compared to chemotherapy alone, while TTF-1-positive patients showed no survival benefit from immunotherapy combinations.
免疫疗法在程序性死亡配体1（PD-L1）阴性的晚期肺腺癌中的疗效仍存在争议，对有反应的亚组特征描述不足。本研究旨在通过甲状腺转录因子1（TTF-1）表达分层来识别预测亚组。
我们回顾性分析了2018年1月至2024年1月期间连续治疗的253例PD-L1阴性晚期肺腺癌患者。比较了接受化疗联合免疫疗法和单纯化疗的TTF-1阳性和TTF-1阴性患者的结局。Cox多变量分析评估了治疗方案的预后影响。
在整个队列中，与化疗相比，化疗联合免疫疗法改善了中位无进展生存期[PFS：7.9对6.6个月，风险比（HR）=0.74，P=0.03]和总生存期（OS：17.5对15.4个月，HR =0.69，P=0.02）。按TTF-1状态分层，接受化疗联合免疫疗法的TTF-1阴性患者（n=66）的PFS（7.5对4.8个月，HR =0.44，P=0.002）和OS（16.2对11.5个月，HR =0.44，P=0.005）显著更优，而TTF-1阳性患者（n=187）的生存无显著差异（PFS：8.0对7.3个月，HR =0.88，P=0.42；OS：18.7对18.3个月，HR= 0.86，P=0.44）。多变量分析证实化疗联合免疫疗法是TTF-1阴性患者的独立有利预后因素[PFS：调整后HR（aHR） =0.44，95%置信区间（CI）：0.24 - 0.81，P=0.008；OS：aHR =0.48，95% CI：0.25 - 0.90，P=0.02]，但在TTF-1阳性队列中无显著关联（PFS：aHR =0.93，95% CI：0.68 - 1.28，P=0.66；OS：aHR =0.91，95% CI：0.62 - 1.35，P=0.64）。
TTF-1表达可能是PD-L1阴性肺腺癌中化疗联合免疫疗法获益的有用预测生物标志物，有待进一步验证。与单纯化疗相比，TTF-1阴性患者接受化疗联合免疫疗法（尤其是基于紫杉烷的方案）生存期改善，而TTF-1阳性患者未从免疫疗法联合治疗中获得生存益处。
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